The leucotrienes have been implicated as mediators of allergic and inflammatory responses associated with bronchial asthma and rheumatoid arthritis. The leucotrienes have been shown to dramatically constrict the pulmonary airways and small blood vessels. In the latter case, increased vascular permeability has been shown to occur after constriction by a leukotriene (Science 215 1380 (1982)).
The study of a series of chromone-2-carboxylic acid derivatives as antagonists of SRS-A (slow reacting substance of anaphylaxis, established by Samuelsson, Department of Chemistry, Karolinska Institutet, Stockholm, Sweden to be one or more leukotrienes--see TIPS, 227, May, 1980) led to the discovery of sodium 7-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropoxy]-4-oxo-8-propyl -4H-1-benzopyran-2-carboxylate (FPL 55712) which proved to be a specific antagonist of SRS-A and a standard for evaluating other inhibitors of SRS-A (J.Med.Chem. 20 371 (1977).
Buckle et al., J.Med.Chem. 22 158 (1979) reported on a number of aryloxyalkyloxy- and aralkyloxy-4-hydroxy-3-nitrocoumarins as antagonists of SRS-A and inhibitors of histamine release. European Pat. No. 0036663 discloses certain oxiranbutyric acid esters as antagonists of SRS-A. U.S. Pat. No. 4,296,237 discloses 3-hydroxy-4-substituted-3-pyrroline-2,5-diones as specific antagonists of SRS-A. U.S. Pat. No. 4,296,120 discloses (carboxy-oxo-pyrrolidino)phenyl alkenamides and esters as SRS-A antagonists. U.S. Pat. No. 4,296,129 discloses (carboxyacylamino)phenyl alkenamides and esters as SRS-A antagonists.